Associations between childhood trauma (CT), social support (SS), brain functions and major depressive disorder (MDD) is unknown.

This study aimed to investigate whether brain functions mediated associations between CT, SS, and MDD.

164 MDD and 98 healthy controls (HC) were recruited and measured by HAMD-24 and HAMA. Some completed CT questionnaire (CTQ) and social support rating scale (SSRS). We examined amplitude of low-frequency fluctuation (ALFF) between the two groups and correlations between HAMD-24, HAMA and ALFF in MDD. Then, the peak voxels of the ALFF changed regions were used as seeds to analyze whole-brain functional connectivity (FC). Next, correlations between FC and clinical variables of MDD were performed. Last, mediation analysis was used to further determine whether ALFF or FC could mediate the associations between CT, SS, and different clinical variables in MDD patients.

Compared to HC, MDD showed decreased ALFF in right posterior cingulate (PCC_R), left postcentral gyrus, right precentral gyrus, and left thalamus (THA_L), but increased ALFF in right medial frontal gyrus, left subgenual anterior cingulate, and left middle occipital gyrus as well as decreased FC in bilateral PCC and THA_R. HAMD-24 had negative correlation with ALFF of THA_L, while positive with sexual abuse (SA) score in MDD. Mediation analysis revealed that FC of PCC_R mediated association between SA and baseline HAMD-24, and itself or together with SS mediated association between CT and onset age of MDD.

CT may influence the depression severity and onset age of MDD by moderating FC of PCC_R only or together with SS.

Major depressive disorder (MDD) is a severe, disabling condition with unknown etiology. Misdiagnosis is common when clinical symptomology criteria are used solely. Considerable evidence suggests that the upregulation of inflammatory factors and cortisol, and a decrease in neurotrophic factors, are involved in the pathogenesis of MDD.

This study explored the application of platforms composed of these serum proteins in the objective diagnosis of MDD.

Serum samples from all participants including 30 MDD patients and 30 well-matched healthy controls were collected at enrollment, eight serum proteins selected initially according to previous studies were analyzed with ELISA. A logistic regression model with these proteins was built to construct the diagnostic platform for the MDD and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of the model.

Among the eight selected proteins, three (TNF-alpha, IL-6 and IL-1beta) were removed because the measurements in more than 1/3 participants were below the detectable limits of ELISA kits. Forward logistic stepwise regression analysis screened out three serum proteins including BDNF, cortisol and IFN-gamma to build the model. The regression equation was Z = 1/[1 + e−(1.438+0.005(BDNF)-0.049(cortisol)-0.007(IFN-gamma))], and the diagnostic efficacy of thees three proteins-combined achieved an area under the ROC curve of 0.884 with sensitivity of 86.7% and specificity of 83.3%.

The results of this study provided a more reliable method to diagnose MDD, and the combination of serum BDNF, cortisol and IFN-gamma may provide an objective diagnostic platform for MDD.

Increasing evidence supports that 5HTTLPR polymorphism of the serotonin transporter gene(5HTTLPR) might associate to bipolar disorder and affective temperaments as measured by TEMPS-A. But the results are discrepant, furthermore, there are no data from Chinese population.

The present study was designed to investigate association between 5HTTLPR and bipolar disorder and affective temperaments of patients with bipolar disorder in the specific Chinese population and add new evidence to the field.

There hundred and five patients with bipolar disorder and 272 normal controls were included in the present case-control study⌧Temperament Evaluation of Memphis, Pisa, Paris and San Diego -autoquestionnaire version (TEMPS-A) in Chinese was used to assess affective temperament. Chi-square test, T test, Nonparametric test and ANOVA were employed to explore association between 5HTTLPR polymorphism and bipolar disorder and affective temperament of patients with bipolar disorder.

5-HTTLPR L/S polymorphism was associated with bipolar disorder in female (genotype χ2 = 6.769⌧P = 0.034⌧allele χ2 = 6.028⌧P = 0.014) and the S allele was associated with anxious temperament (t = 8.248⌧P = 0.005) in patients with bipolar disorder. the LA allele of 5-HTTLPR rs25531 A/G polymorphism was associated with hyperthymic temperament in patients with bipolar disorder (Z = −2.205⌧P = 0.027).

5-HTTLPR might have an effect on the prevalence of bipolar disorder in female and regulate affective temperaments of patients with bipolar disorder in some degree in Chinese population.

rs10761482 in ANK3 gene showed a significant association with schizophrenia in a genome-wide association study (GWAS). Another marker rs10994336 in ANK3 with the risk of bipolar disorder (BD) which might have more genetic overlap with schizophrenia, had been reported in two meta-analyses of GWAS. In this study, we investigated the association between ANK3 polymorphisms and the susceptibility of schizophrenia in Chinese Han population.

Population-based (schizophrenia patients = 516 and controls = 400) and family based (trios of early onset schizophrenia= 81) study was performed through genotyping the most promising makers rs10761482, rs10994336, and two missenses rs3808942 and rs3808943 near promoter of ANK3. Particularly, we conducted an association analysis for the combined case-control and family samples.

Our population-based study replicated the association between rs10761482 (P = 0.0268 with C allele) and schizophrenia, and detected a novel association with rs10994336 (P = 4.0 × 10−4 with T allele). Haplotype analysis revealed the higher frequencies of C-T, and T-C (rs10761482–10994336) in the cases than controls (P = 0.0032 and P = 0.0012, respectively). In the family study, the C allele of rs10761482 (P = 0.0940) and T allele of rs10994336 (P = 0.0832) were slightly over-transmitted, and T-C was significantly associated with schizophrenia (P = 0.0304). The results from the combined samples analysis were consistent with independent analysis. rs10761482, rs10994336, C-T, and T-C were significantly associated with schizophrenia (P = 3.3 × 10−6∼3.9 × 10−5), whilst rs3808942 and rs3808943 did not reach normal significance.

Our data strongly support ANK3 gene is a schizophrenia susceptibility gene, and also provide further evidence for the shared susceptibility loci between schizophrenia and BD.

rs10761482 in ANK3 gene showed a significant association with schizophrenia in a genome-wide association study (GWAS). Another marker rs10994336 in ANK3 with the risk of bipolar disorder (BD) which might have more genetic overlap with schizophrenia, had been reported in two meta-analyses of GWAS.

In this study, we investigated the association between ANK3 polymorphisms and the susceptibility of schizophrenia in Chinese Han population.

Population-based (schizophrenia patients = 516 and controls = 400) and family based (trios of early onset schizophrenia= 81) study was performed through genotyping the most promising makers rs10761482, rs10994336, and two missenses rs3808942 and rs3808943 near promoter of ANK3. Particularly, we conducted an association analysis for the combined case-control and family samples.

Our population-based study replicated the association between rs10761482 (P = 0.0268 with C allele) and schizophrenia, and detected a novel association with rs10994336 (P = 4.0 × 10−4 with T allele). Haplotype analysis revealed the higher frequencies of C-T, and T-C (rs10761482–10994336) in the cases than controls (P = 0.0032 and P = 0.0012, respectively). In the family study, the C allele of rs10761482 (P = 0.0940) and T allele of rs10994336 (P = 0.0832) were slightly over-transmitted, and T-C was significantly associated with schizophrenia (P = 0.0304). The results from the combined samples analysis were consistent with independent analysis. rs10761482, rs10994336, C-T, and T-C were significantly associated with schizophrenia (P = 3.3 × 10−6∼3.9 × 10−5), whilst rs3808942 and rs3808943 did not reach normal significance.

Our data strongly support ANK3 gene is a schizophrenia susceptibility gene, and also provide further evidence for the shared susceptibility loci between schizophrenia and BD.

Bioinformatic investigations indicate that has-mir-206 (microRNA-206, miRNA-206) could regulate BDNF protein synthesis by interfering with BDNF mRNA translation, which is disrupted in bipolar disorder (BPD).

This study is to investigate whether miRNA-206 gene variants were associated with BPD susceptibility in a Han Chinese population.

342 patients who met DSM-IV criteria for bipolar disorder type I (BPD-I) or type II (BPD-II) and 386 matched health controls were enrolled into this study. the miRNA-206 gene and +/-500bp were selected for gene sequencing. for the case-control genetic comparisons, differences in the genotype and allele distributions between patients and controls were examined using Pearson's χ2 test.

Gene sequencing showed that there are two polymorphisms rs16882131(C/T) and rs62408583 (A/C) located at the upstream of miRNA-206 gene, which are complete linkage disequilibrium. the association analysis showed that there was no significant difference for genotype frequencies (χ2 = 2.075, df = 2, P = 0.354) or for allele frequencies (χ2 = 0.041, df = 1, P = 0.839) between BPD patients and controls. Similarly, no significant difference was found between BPD-I patients and controls (genotype χ2 = 1.411, df = 2, P = 0.494; allele χ2 = 0.380, df = 1, P = 0.538). However, there was significant difference between BPD-II patients and controls (genotype χ2 = 7.933, df = 2, P = 0.019; allele χ2 = 5.403, df = 1, P = 0.020).

Our findings do not support that BPD susceptibility was associated with miRNA-206 gene polymorphisms in the studied Han Chinese population. the association between miRNA-206 gene polymorphisms and bipolar disorder type II is needed to be carefully interpreted. Further studies are necessary to elucidate the involvement miRNA-206 in the pathophysiology of BPD.

To explore the difference in the clinical features between bipolar disorder and unipolar depression from the clinical phenomenology.

Two hundred bipolar patients with their current depressive episode and five hundred and sixty three recurrent depression were involved in the study. Clinical features of these two groups were compared and stepwise Logistic regression was used to identify the relationship between clinical features and bipolar disorder.

Clinical features of depressive episode which was different between two groups and were associated with bipolar disorder were as follows: age at onset of bipolar was earlier than that of unipolar depression; Bipolar patients whose age at onset before 25 years were more than unipolar depression; Sexual appetites which was one of atypical depressive symptoms were more common in bipolar depression than in unipolar depression; with psychiatric symptoms, psychomotor retardation, mood instability and duration of every depressive episode < 3 months, were more common in bipolar depression group than in unipolar depression group; Cognitive impairment factor, one of factors of HAMD-17 score, was significantly higher in bipolar depression group than in unipolar depression group. The odd ratio were 1.54, 1.50, 3.25, 1.99, 1.89, 1.48, 1.63, 1.63, and 1.42 separately.

The founding suggested that unipolar depression and bipolar depression might be distinct disorder, and age at onset, age at onset < 25, sexual appetites, psychiatric symptoms, psychomotor retardation, mood instability and duration of every depressive episode < 3 months might be potential to be the predictors of bipolar disorder.

To explore the factors associated with occurrence of suicidal risk after treatment of SSRI in bipolar disorder with their first depressive episode.

One hundred and seventy seven bipolar patients were enrolled in this retrospective study. One hundred fifty four patients were included in non-occurrence of suicidal risk group, while twenty three were included in occurrence of suicidal risk group. To compare the demographic and clinic features between these two groups. Stepwise Logistic regression model was used to identify the associated factors. Concordance statistics (i.e. the area under the ROC curve) was used to compute the discrimination of the associated factors, and Hosmer-Lemeshow goodness-of-fit statistic was used to measure the goodness-of-fit.

Clinical features associated with occurrence of suicidal risk after treatment of SSRI in bipolar disorder were as follows: psychotic symptom and symptom of irritability. The odd ratio was 6.23 and 4.04 separately.

This study demonstrated indicated that psychotic symptom and symptom of irritability were associated with occurrence of suicidal risk after treatment of SSRI in bipolar disorder, and it suggested that these two symptoms might be potential to be the predictors of occurrence of suicidal risk after treatment of SSRI in bipolar disorder.

Major depressive disorder (MDD) is associated with abnormal functional connectivity (FC) of amygdala and decreased function of cortico-limibic circuit, which play important roles in the pathogenesis of MDD. However, little is known about the connectivity alterations in late-onset depression (LOD), and whether such disrupted function is correlated with cognitive impairment is unclear.

A total of twenty-three LOD patients and thirty-seven controls underwent neuropsychological tests and resting-state functional magnetic resonance imaging (RS-fMRI). Regional homogeneity (ReHo) and FC of bilateral amygdala seed were used to analyze blood oxygen level-dependent fMRI data between groups.

Compared to controls, LOD groups showed weaker functional activity in bilateral middle frontal gyrus and left medial orbitofrontal gyrus, moreover, the decreased ReHo was positively correlated with Trail making test-B score (TMTB, r= 0.462,P= 0.04). In aspects of FC, left amygdala has reduced FC with right fusiform gyrus, right superior temporal gyrus and right putamen, while right amygdala has reduced FC with left cerebellum. Further correlative analysis found that the decreased FC between amygdala and right putamen was positively correlated with Verbal fluency test-verb score (VFT-verb, r= 0.513,P= 0.021) and the decreased FC between amygdala and superior temporal gyrus was positively correlated with Auditory Verbal Memory Test-delayed recall score (AVLT-delayed recall, r= 0.446,P= 0.049).

Our finding of reduced activation of prefrontal gyrus as well as decreased connection of bilateral amygdala may be key factors of impaired cognitive function in LOD patients and these changes could be early indicator for cognitive deficits.

The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among patients with SSD, major depressive disorder (MDD) and healthy controls.

Gene expression profiling was conducted in peripheral blood leucocytes from drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group) using global mRNA expression arrays. Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step.

We identified SSD and MDD gene signatures from blood-based gene expression profile and build a SSD- MDD disorder model with higher predictive power. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P <= 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy.

Blood cell-derived RNA may have significant value for performing diagnostic functions and identifying disease biomarkers in SSD and MDD. These 48 gene model could classify SSD, MDD, and healthy controls.

To study the relationship between insulin-like growth factor 1 receptor (IGF1R)and subsyndromal symptomatic depression (SSD).

In this case-control study, real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) with TaqMan MGB was used to analyzing the differences of IGF1R gene mRNA expression in peripheral leukocytes between subsyndromal symptomatic depression group(n = 47) and healthy controls(n = 52). At the same time Hamilton Depression Rating Scale -17(HAMD17) were assessed.

IGF1R gene mRNA expression was 0.21 ± 0.11 in SSD group, 0.56 ± 0.37 in healthy group, and there was significant difference between both groups on IGF1R expression(z = 39.54, P < 0.001). the expression levels of IGF1R in SSD patients was not correlated with Hamilton score(r = −0.292, p = 0.275).

This study suggested that the decreased expression of IGF1R were related with the pathophysiology of SSD.

Epigenetic changes may play a role in the etiology of psychotic diseases. It has been demonstrated that olig2 is implicated in schizophrenia (SCZ) and bipolar disorder (BPD). the aim of this study was to investigate the methylation status of a promoter region of the olig2 gene in BPD and SCZ patients.

Our study included 41 BPD and 45 SCZ (DSM-IV criteria) as well as 53 control subjects. DNA was extracted from blood leukocytes and bisulfited sequence analysis was used to determine the DNA methylation status of a typical CpGs island within the promoter region of olig2.

We found the methylated cytosines occurred mainly in two clusters. Olig2 gene promoter was hyper-methylated(∼30%) in DNA derived from the blood leukocytes in SCZ and BD compared to the controls subjects(P = 0.01 and P = 0.03, respectively). There was no statistically significant difference in frequency of site-specific cytosine methylation modification of Olig2 gene between SCZ patients and BD patients(P = 0.21).

We observed increased DNA methylation in the promoter region of the olig2 gene of SCZ and BPD. This could explain the reported decrease of the gene expression. the current study supports the growing interest of DNA methylation in psychopathology.

The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.

Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.

We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).

Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.